PDF(Pubmed)
Abstract：
Despite advancements in genetic and functional studies, the timely diagnosis of common variable immunodeficiency (CVID) remains a significant challenge. This exploratory study was designed to assess the diagnostic performance of a novel panel of biomarkers for CVID, incorporating the sum of κ+λ light chains, soluble B-cell maturation antigen (sBCMA) levels, switched memory B cells (smB) and the VISUAL score. Comparative analyses utilizing logistic regression were performed against established gold-standard tests, specifically antibody responses. Our research encompassed 88 subjects, comprising 27 CVID, 23 selective IgA deficiency (SIgAD), 20 secondary immunodeficiency (SID) patients and 18 healthy controls. We established the diagnostic accuracy of sBCMA and the sum κ+λ, achieving sensitivity (Se) and specificity (Spe) of 89% and 89%, and 90% and 99%, respectively. Importantly, sBCMA showed strong correlations with all evaluated biomarkers (sum κ+λ, smB cell and VISUAL), whereas the sum κ+λ was uniquely independent from smB cells or VISUAL, suggesting its additional diagnostic value. Through a multivariate tree decision model, specific antibody responses and the sum κ+λ emerged as independent, signature biomarkers for CVID, with the model showcasing an area under the curve (AUC) of 0.946, Se 0.85, and Spe 0.95. This tree-decision model promises to enhance diagnostic efficiency for CVID, underscoring the sum κ+λ as a superior CVID classifier and potential diagnostic criterion within the panel.
摘要：
尽管基因和功能研究取得了进展，常见变异型免疫缺陷(CVID)的及时诊断仍是一项重大挑战.这项探索性研究旨在评估一组新型的CVID生物标志物的诊断性能，结合κ+λ轻链的总和，可溶性B细胞成熟抗原（sBCMA）水平，转换记忆B细胞(smB)和视觉评分。利用逻辑回归进行比较分析，以建立黄金标准测试，特别是抗体反应。我们的研究涵盖了88个主题，包括27个CVID，23选择性IgA缺乏症（SIGAD），20例继发性免疫缺陷（SID）患者和18例健康对照。我们建立了sBCMA的诊断准确性和κ+λ的总和，实现89%和89%的灵敏度(Se)和特异性(Spe)，90%和99%,分别。重要的是,sBCMA与所有评估的生物标志物显示出强相关性(总和κ+λ，smB细胞和视觉)，而κ+λ的总和是唯一独立于smB细胞或VISUAL的，提示其额外的诊断价值。通过多变量树决策模型，特异性抗体反应和κ+λ的总和是独立的，CVID的特征生物标志物，该模型显示曲线下面积（AUC）为0.946，Se0.85和Spe0.95。这种树决策模型有望提高CVID的诊断效率，强调和κ+λ作为面板内优越的CVID分类器和潜在的诊断标准。
